| Acute ST elevation myocardial infarction(STEMI) is a serious clinical types of coronary heart disease. STEMI is mainly triggered by the coronary atherosclerotic plaque rupture, leading to platelet activation and blood coagulation, which cause thrombosis and block coronary artery. Early positive opening of infarct related artery and restoring effective myocardial reperfusion can reduce mortality and decrease the complications in patients with acute myocardial infarction. Benefits of early reperfusion in patients presenting with STEMI are well known. Improvement of myocardial reperfusion with a greater use of primary percutaneous coronary intervention, adjunctive pharmacological and mechanical therapies have contributed to a spectacular decrease in mortality of patients presenting with STEMI. Inducing angiogenesis and accelerating the establishment of collateral circulation can be used as a treatment strategy for myocardial and limb ischemia which are caused by coronary and peripheral artery atherosclerosis.Microparticles (MPs) are vesicles less than 1 mm in diameter shed from the plasma membranes of cells that are injured, activated, or undergoing apoptosis. MPs found in the plasma originate predominantly from platelets and less so from other cells such as endothelial cells, leukocytes, and erythrocytes. Many articles have described the involvement of MPs in the processes of vascular dysfunction, atherosclerosis, thrombosis, and angiogenesis well as their association with various conditions related to cardiovascular disease (CVD). MPs was especially concerned for their roles in cardiovascular system. Platelet-derived MPs have been shown to induce angiogenesis in vitro and to stimulate post-ischemic myocardial revascularization. Injection of PMPs into the ischemic myocardium might improve the process of revascularization after chronic ischemia. MPs produced during tissue ischemia promote neovascularization. These results suggest that MPs could act as endogenous survival signals responsible for vascular repair.MPs also significantly increase in patients with STEMI. But there is no literature reported so far about MPs in infarcted coronary microenvironment of STEMI patients. Existing studies have shown the contribution of MPs in angiogenesis. However, it is not clear now whether coronary MPs can promote angiogenesis.In present study, we therefore investigated whether the numbers of coronary MPs were different with circulating MPs, if coronary MPs had a role in stimulating angiogenesis, and further we studied the mechanism. Sample analysis experiment: collecting basis conditions and laboratory test results of patients with STEMI who undergoing emergency PCI. Before the surgery,5 ml blood samples were collected from infarcted coronary and aorta where punctured. MPs were separated and extracted from the blood samples. Coronary MPs had higher level than Circulating MPs by flow cytometry. In addition, the level of PMPs and EMPs increased, but there was no difference in PMPs level. In vitro, Circulating MPs and Coronary MPs from patients with STEMI were non-toxic to HUVECs and couldn’t promote proliferation. Compared with Circulating MPs, we found Coronary MPs promote cell migration measured by the scratch test and transwell experiment. Coronary MPs could also stimulate angiogenesis by capillary-like structure formation experiment. Control, Circulating Sn and Coronary Sn had no effect on cell migration and angiogenesis. After further exploring the mechamisms of Coronary MPs, we also found Coronary MPs activated phosphorylation of eNOS Ser1177 residue and phosphorylation of AKT Ser 473 residue by western blot, but not altered eNOS and AKT protein expression, compared with Circulating MPs. LY294002(PI3K/AKT pathway inhibitor), L-NAME(NOS inhibitor), siRNA-PI3Kp85a and siRNA-eNOS inhibited the cell migration and angiogenesis promoted by Coronary MPs. The inhibitor LY294002 and siRNA-PI3Kp85a also inhibited the phosphorylation of eNOS Ser1177 and AKT Ser473 triggered by Coronary MPs. Coronary MPs increased the content of NO and VEGF in cell culture supernatant using kit and ELISA. Aortic ring assay:Endothelium-dependent relaxation in aortic rings from ICR mices showed Coronary MPs do not impair endothelium-dependent relaxation, there was no significant difference between Coronary MPs and MPs from peripheral blood in healthy volunteers.These results indicate that the level of Coronary MPs is higher than Circulating MPs. Coronary MPs do not trigger proliferation, they can promote cell migration and stimulate angiogenesis through PI3K/AKT/eNOS/VEGF signaling pathway. Coronary MPs do not cause endothelial dysfunction in aortic rings from ICR mices. All these results provide a solid reaserch basis for the wildly use and potential applications of MPs in the treatment of STEMI. |
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